Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-kappaB Pathways in Nasal Fibroblasts
Allergy, Asthma & Immunology Research
;
: 567-572, 2014.
Artículo
en Inglés
| WPRIM
| ID: wpr-183727
ABSTRACT
PURPOSE:
Based on the close relationship between histamine and interleukin 6 (IL-6), we hypothesized that histamine may regulate the production of cytokines, such as IL-6, during allergic inflammation. Here, we examined the role of histamine in IL-6 production and histamine receptor activity in nasal fibroblasts, along with the mechanisms underlying these effects.METHODS:
Experiments were performed using nasal fibroblasts from 8 normal patients. RT-PCR was used to identify the major histamine receptors expressed in nasal fibroblasts. Fibroblasts were then treated with histamine with or without histamine-receptor antagonists, and monitored for IL-6 production using an ELISA. Four potential downstream signaling molecules, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-kappaB, were evaluated by Western blot, and a luciferase reporter assay.RESULTS:
Elevated expression was seen for all histamine receptors, with IL-6 protein levels increasing significantly following histamine stimulation. Among the histamine-receptor specific antagonists, only the H1R antagonist significantly decreased IL-6 production in histamine-stimulated nasal fibroblasts. Histamine increased the expression level of phosphorylated p38 (pp38), pERK, and pJNK, as well as NF-kappaB induction. The H1R antagonist actively suppressed pp38 and NF-kappaB expression in histamine-induced nasal fibroblasts, but not pERK and pJNK. The p38 inhibitor strongly attenuated IL-6 production in histamine-stimulated nasal fibroblasts.CONCLUSIONS:
The data presented here suggest that antihistamines may be involved in the regulation of cytokines, such as IL-6, due to the role of histamine as an inflammatory mediator in nasal fibroblasts.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Fosfotransferasas
/
Ensayo de Inmunoadsorción Enzimática
/
Receptores Histamínicos
/
Histamina
/
Nariz
/
Western Blotting
/
Citocinas
/
FN-kappa B
/
Interleucina-6
/
Proteínas Quinasas JNK Activadas por Mitógenos
Tipo de estudio:
Estudio pronóstico
Límite:
Humanos
Idioma:
Inglés
Revista:
Allergy, Asthma & Immunology Research
Año:
2014
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS